构建靶向型Pluronic F127/芒柄花黄素纳米复合体系体外抗肝癌活性  

Anti-hepatoma activity of targeted Pluronic F127/formononetin nanocomposite system in vitro

作　　者：柳扬[1] 龚毅[1] 范伟[1] Liu Yang;Gong Yi;Fan Wei(Second Department of Hepatobiliary Surgery,Guizhou Provincial People’s Hospital,Guiyang 550002,Guizhou Province,China)

机构地区：[1]贵州省人民医院肝胆外科二部,贵州省贵阳市550002

出　　处：《中国组织工程研究》2021年第4期526-531,共6页Chinese Journal of Tissue Engineering Research

基　　金：2016年度贵阳市科技计划项目(20161001),项目负责人:范伟。

摘　　要：背景:天然黄酮类化合物芒柄花黄素是传统中药提取物,具有抗癌作用,但疏水性结构、体内代谢周期短限制了其临床应用。目的:制备负载芒柄花黄素的Pluronic F127-叶酸共轭胶束,检测其体外释药性能与抗癌活性。方法:采用碳二亚胺交联剂化学方法制备叶酸偶联的Pluronic F127(PF-FA),采用薄膜水化法制备负载芒柄花黄素的Pluronic F127胶束(FN-PF)与负载芒柄花黄素的Pluronic F127-叶酸共轭胶束(FN-PF-FA),检测FN-PF与FN-PF-FA胶束的包封率、载药量与体外释药性能。采用体外硫荷达明B实验检测游离芒柄花黄素、FN-PF胶束、FN-PF-FA胶束对叶酸过表达人肝癌HepG2细胞的体外抗癌活性。结果与结论:①FN-PF和FN-PF-FA胶束的包封率分别为(84.12±2.15)%和(82.50±1.78)%,载药量分别为(21.33±2.27)%和(19.73±1.58)%;②两种胶束在酸性环境中的释药速率均快于碱性环境;在相同环境中,FN-PF-FA胶束的释药速率慢于FN-PF胶束;③在相同的药物浓度下,FN-PF胶束、FN-PF-FA胶束抑制人肝癌HepG2细胞增殖的能力强于游离的芒柄花黄素(P<0.05),并且FN-PF-FA胶束的抑制作用强于FN-PF胶束(P<0.05);④抑制肿瘤所需的药物浓度顺序为FN-PF-FA胶束<FN-PF胶束<游离的芒柄花黄素,组间比较差异有显著性意义(P<0.01);⑤结果表明,FN-PF-FA胶束具有靶向抗癌药物释放的潜力。BACKGROUND:Natural flavonoid formononetin(FN)is traditional Chinese medicine extract and has anticancer effect,but the hydrophobic structure and short half-life in vivo limit their clinical applications.OBJECTIVE:To prepare FN loaded pluronic(PF)-folic acid(FA)conjugated micelles(FN-PF-FA)and to test in vitro drug release and anticancer activity.METHODS:FA coupling PF was prepared by carbodiimide crosslinker chemical method.FN-PF-FA micelles were prepared by film hydration method.The encapsulation efficiency,drug loading and drug release performance of FN-PF and FN-PF-FA micelles were measured.The in vitro anti-cancer activity of flavin,FN-PF micelles,and FN-PF-FA micelles on folic acid-overexpressing human liver cancer HepG2 cells was measured by in vitro thiohodamine B experiment.RESULTS AND CONCLUSION:(1)The encapsulation efficiency of FN-PF and FN-PF-FA micelles was(84.12±2.15)%and(82.50±1.78)%,respectively,and the drug loading was(21.33±2.27)%and(19.73±1.58)%,respectively.(2)The release rate of both micelles in acidic environment was faster than that in alkaline environment.In the same condition,the release rate of FN-PF-FA micelles was slower than that of FN-PF micelles.(3)At the same drug concentration,the ability of FN-PF micelles and FN-PF-FA micelles to inhibit the proliferation of human liver cancer HepG2 cells was stronger than that of free FN(P<0.05).Moreover,the inhibitory effect of FN-PF-FA micelles was stronger than that of FN-PF micelles(P<0.05).(4)The order of drug concentration required to inhibit tumors was FN-PF-FA<FN-PF<free FN,and there was a significant difference between groups(P<0.01).(5)Results suggested that FN-PF-FA micelles had the potential to target the release of anticancer drugs.

关 键 词：材料 纳米 靶向 肝癌 叶酸 胶束 释药 

分 类 号：R459.9[医药卫生—治疗学] R318.08[医药卫生—临床医学]